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CARDIOVASCULAR ANESTHESIA

Fast-Track Cardiac Anesthesia: Use of Remifentanil Combined with Intrathecal Morphine as an Alternative to Sufentanil During Desflurane Anesthesia

Department of Anesthesiology and Pain Management, University of Texas, Southwestern Medical Center at Dallas, Dallas, Texas

Address correspondence to Paul F. White, PhD, MD, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., F2.208, Dallas, TX 75235-9068. Address e-mail to paul.white{at}email.swmed.edu

	Abstract

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The purpose of this cardiac fast-track study was to evaluate the use of remifentanil (R) combined with intrathecal (IT) morphine as an alternative to sufentanil (S) during desflurane anesthesia with respect to postoperative pain control. Prior to entering the operating room, patients in the R group (n = 20) received morphine, 8 µg/kg IT. Anesthesia was induced using a standardized anesthetic technique in all patients. In the R group, anesthesia was maintained with R, 0.1 µg · kg^-1 · min^-1 in combination with desflurane 3–10%. In the S group (n = 20), patients received S 0.3 µg · kg^-1 · h^-1 and desflurane 3–10%. There were no differences between the two groups with respect to time from arrival in the intensive care unit to tracheal extubation (5.1 ± 4.3 h vs 5.8 ± 6.7 h for R and S groups, respectively). After extubation, patients in the R group had significantly lower visual analog pain scores, reduced patient-controlled analgesic requirements, and greater satisfaction with their perioperative pain management, compared with patients in the S group. We conclude that R combined with IT morphine provided superior pain control after cardiac surgery compared with a S-based general anesthetic technique.

Implications: As part of a cardiac fast-tracking program involving desflurane anesthesia, the use of intrathecal morphine in combination with a remifentanil infusion provided improved postoperative pain control, compared with IV sufentanil alone.

	Introduction

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Fast-track cardiac anesthetic techniques can lead to earlier tracheal extubation, shorter intensive care unit (ICU) stays, and significant reductions in perioperative costs and resource utilization (1,2). Whereas large-dose IV opioid techniques provide excellent intraoperative hemodynamic stability and postoperative analgesia, extubation times are often prolonged (3,5). The use of smaller doses of opioid analgesics in combination with volatile anesthetics facilitates earlier tracheal extubation at the expense of increased postoperative pain (4,5).

Intrathecal (IT) morphine produces prolonged postoperative analgesia when administered to patients undergoing cardiac surgery (6,7). However, when IT morphine was combined with smaller doses of fentanyl for fast-track cardiac anesthesia, significant prolongation of the extubation time has been reported (8). Although the ultra-short-acting opioid remifentanil can provide excellent hemodynamic stability during cardiac surgery, minimal residual analgesia in the postoperative period has discouraged its use as part of cardiac fast-tracking protocols.

This study was designed to compare IV remifentanil combined with IT morphine to IV sufentanil when administered as a supplement to desflurane anesthesia with respect to the quality of recovery and adequacy of pain management as part of a fast-track cardiac surgery program.

	Methods

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After institutional review board approval and written informed consent, 40 adult patients scheduled for elective coronary artery bypass grafting or valve replacement surgery participated in this study. Subjects were randomly assigned to one of two anesthetic treatment groups using a computer-random number table. Patients with a left ventricular ejection of less than 20%; those requiring preoperative IV inotropic drugs, intraaortic balloon support, or mechanical ventilation; and those with significant pulmonary, endocrine, metabolic, or neurologic pathology were excluded. Patients with a platelet count of less than 150,000/mm3, or those receiving preoperative heparin, were also excluded. Patients who were receiving medications known to affect coagulation or who had a history of abnormal bleeding were included only after documentation of a normal prothrombin time, a normal partial thromboplastin time, and a normal bleeding time.

After IV sedation with midazolam 2–5 mg IV, a 20-gauge radial artery catheter was placed. Patients in the remifentanil group received an injection of IT morphine, 8 µg/kg, at the L 2–3 or L 3–4 interspace using a 25-gauge pencil-point needle. If the investigator was unable to obtain clear cerebrospinal fluid or the procedure required more than 15 min, the patient was withdrawn from the study and the case proceeded without IT opioids. No additional premedication was administered to patients in either treatment group.

Anesthesia was induced in both groups with sufentanil, 0.75 µg/kg, followed by etomidate, 0.25 mg/kg IV, and tracheal intubation was facilitated with rocuronium, 1 mg/kg IV. Maintenance of anesthesia consisted of either a remifentanil infusion, 0.1 µg · kg^-1 · min^-1 and desflurane 3–10% (inspired) or sufentanil infusion, 0.3 µg · kg^-1 · h^-1 and desflurane 3–10% (inspired). In both groups, the inspired desflurane concentration was varied to maintain the mean arterial pressure within 20% of the preinduction baseline values. Remifentanil and sufentanil infusions were continued throughout the operation, and desflurane was also administered via the cardiopulmonary bypass circuit. Separation from cardiopulmonary bypass was accomplished using standard inotropic and/or vasoactive drugs. Hemodynamic data were recorded at 5-min intervals by an individual not involved in the patient’s anesthetic care.

Prior to transfer from the operating room to the ICU, the desflurane/sufentanil or remifentanil infusion was discontinued and a propofol infusion started at 25 µg · kg^-1 · min^-1. In the ICU, the nursing staff administered incremental doses of hydromorphone, 150 µg IV, for acute pain control prior to tracheal extubation. Forced air warming was used to maintain the patient’s core temperature between 36.5°–37.5°C, and shivering was treated with meperidine, 25 mg IV. The propofol infusion was discontinued when the patient had acceptable ventilatory parameters (FIO₂ < 60%, peak end-expiratory pressure < 7.5 cm H₂O, PO₂ > 90 mm Hg) during synchronized intermittent mandatory ventilation, was hemodynamically stable, and was normothermic (core temperature > 36°C). Tracheal extubation occurred when the patient met the following criteria: patient awake, oriented, and cooperative; chest tube output < 100 mL/h; absent arrhythmias; urine output > 0.5 mL · kg^-1 · h^-1, absence of muscle relaxation and adequate ventilatory parameters (vital capacity > 12 mL/kg, respiratory rate > 10 bpm, minute ventilation > 90 mL · kg^-1 · min^-1, FIO₂ < 0.6, peak end-expiratory pressure < 7.5 cm H₂O, PO₂ > 90 mm Hg). Arterial blood gas values were assessed before extubation and at 30 min and 4 h after extubation. Respiratory rate was measured at 1- to and 5-h intervals after extubation.

After extubation, the patients used a patient-controlled analgesia device to deliver 150 µg IV boluses of hydromorphone "on demand" at minimum intervals of 10 min. The ICU and surgical staff made decisions regarding the administration of postoperative inotropes, vasodilators, and/or vasoconstrictors, as well as pulmonary artery catheter and chest tube removal. ICU discharge criteria included patient orientation with minimum sedation, hemodynamic stability without the use of IV inotropes, SpO₂ > 90% with a FIO₂ of <0.6, absent CO₂ retention, urine output > 0.5 mL · kg^-1 · h^-1, and a chest tube output < 50 mL · h^-1. Postoperative nausea and vomiting and pruritis were treated with ondansetron, 4 mg IV, and nalbuphine, 5 mg IV, respectively.

Postoperative evaluations were performed at 1-, 2-, 4-, 8-, 12-, 24-, and 48-h intervals after tracheal extubation, including assessments of the level of sedation using the Ramsay scale (9) and pain scores using a 100-mm visual analog scale, where 0 = no pain and 100 = severe pain. Patients were also directly questioned regarding the occurrence of pruritis, nausea, and vomiting. Urinary retention was defined as the need for reinsertion of a bladder catheter because of inability to void after its removal. The time from arrival in the ICU to pulmonary artery catheter and chest tube removal, discharge from the ICU, ambulation, and discharge from the hospital were also recorded. At 24 and 48 h after discharge from the ICU, a structured interview was conducted to investigate intraoperative recall and to assess the adequacy of postoperative pain management (Appendix I).

Data were analyzed with the NCSS 6.0^TM statistical analysis program (NCSS, Kaysville, UT). An a priori power analysis indicated that a sample size of 20 patients in each group should be adequate to detect a 30% change in the postoperative opioid analgesic requirements with a power of 0.8 ( = 0.05). One-way analysis of variance was performed for all continuous variables. When a significant difference was noted, Neuman-Keuls or Duncan tests were performed for post-hoc comparisons within, as well as between groups. Nonparametric variables were analyzed using the 2 test or Fisher’s exact test. Differences were considered statistically significant if the P value was <0.05. Values are expressed as the mean ± SD.

	Results

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Demographic characteristics, the type of cardiac surgical procedures, ASA physical status, anesthesia times, and intraoperative opioid dosages are summarized in Table 1. The mean time required for lumbar puncture was 13 ± 6 min in the remifentanil group. There were no intraoperative differences in heart rate, mean arterial pressure, pulmonary artery pressure, central venous pressure, or cardiac output between the two groups (data not reported). The average end-tidal desflurane concentration during the maintenance period was similar in both groups (3.43% and 3.96% in the remifentanil and sufentanil groups, respectively). The mean ± SD times to tracheal extubation also were similar at 5.1 ± 4.3 h and 5.8 ± 6.7 h in the remifentanil and sufentanil groups, respectively. There were no significant differences in ischemic episodes or troponin levels in the postoperative period (Table 1). The arterial blood gas values before tracheal extubation and at 30 min and 4 h after extubation were similar in the two treatment groups. Finally, the respiratory rate and Ramsay sedation scale scores were also similar between the two groups during the first 24 h after extubation.

View larger version (43K): [in this window] [in a new window]   Figure 1. Visual analog scale (VAS) pain scores for the remifentanil-IT (intrathecal) morphine and sufentanil-treated patients at specific intervals after tracheal extubation, with 0 = no pain and 100 = the worst pain imaginable. VAS scores differed significantly between the two groups at all time points after extubation. Values are means ± SD.

View larger version (38K): [in this window] [in a new window]   Figure 2. Cumulative dosages of hydromorphone delivered by a patient-controlled analgesia device in the remifentanil-IT (intrathecal) morphine and sufentanil groups at specific intervals after tracheal extubation. Doses differed significantly between the two groups at all time points after extubation. Values are means ± SD. mcg = µg.

	Discussion

Top Abstract Introduction Methods Results Discussion Appendix 1 References

The administration of IT morphine prior to cardiac surgery can provide residual analgesia in the postoperative period. In placebo-controlled studies, Chaney et al. (6) and Vanstrum et al. (7) demonstrated that the administration of IT morphine (52 and 6 µg/kg, respectively) immediately prior to induction of anesthesia significantly decreased postoperative analgesic requirements. On the other hand, Casey et al. (13) reported that administration of IT morphine (20 µg/kg) immediately after tracheal extubation did not decrease postoperative analgesic requirements. In this study, IT morphine, 8 µg/kg, provided effective postoperative analgesia, as indicated by a significant decrease in postoperative IV hydromorphone requirements, lower VAS pain scores, and improved patient satisfaction. At 24 h postoperatively, the total opioid analgesic use was decreased by 80% in the remifentanil-IT morphine group, compared with the sulfentanil-based general anesthetic technique. In addition, the patients in the remifentanil-IT morphine group were more likely to rate their pain management as "excellent" and their sleep had not been disturbed by the need for pain control.

Although IT morphine can provide excellent postoperative analgesia, concerns have been raised regarding the potential for ventilatory depression and delayed extubation when used as part of a fast-tracking program. For example, Chaney et al. (8) demonstrated significant prolongation of the time until tracheal extubation in patients receiving IT intrathecal morphine (10 µg/kg) combined with systemic fentanyl (20 µg/kg). These investigators concluded that long-acting IT and IV opioid analgesics increased the risk of ventilatory depression after cardiac surgery. However, others have reported that smaller intraoperative doses of IV fentanyl (2–4 µg/kg), followed by IT morphine (10 µg/kg) allowed extubation in the operating room after thoracotomy procedures without increasing the incidence of postoperative respiratory complications (14). Since the residual ventilatory depression produced by an ultra-short acting opioid like remifentanil should be minimal, use of IT morphine should facilitate the fast-tracking process when remifentanil is used as the primary analgesic during cardiac surgery. Our study demonstrated that IT morphine (8 µg/kg) administered prior to cardiac surgery in combination with systemic remifentanil, 0.1 µg · kg^-1 · min^-1 did not delay extubation when compared with systemic sufentanil, 0.3 µg · kg^-1 · h^-1.

The study design could be criticized because the remifentanil infusion rate was lower than the dosage administered in earlier clinical trials (15,16). However, we have recently demonstrated that remifentanil infusion rates of 0.07–0.09 µg · kg^-1 · min^-1 can decrease the volatile anesthetic requirement by 47–54% (17,18). Although the selection of a fixed dose of each opioid analgesic could be criticized, both opioid groups required similar end-tidal concentrations of desflurane to maintain hemodynamic stability during the operation.

In the sufentanil (control) group, the administered dose of the opioid has been shown to facilitate early extubation after cardiac surgery (19). Propofol was used for sedation in both groups during the early postoperative period because it facilitates the process of weaning patients from mechanical ventilation after cardiac surgery when compared with midazolam (19,20). The incidence of postoperative, opioid-related side effects (e.g., nausea and vomiting, pruritis, and urinary retention) were small, and no differences were noted between the two treatment groups.

In conclusion, the use of IT morphine, 8 µg/kg, in combination with IV remifentanil, 0.1 µg · kg^-1 · min^-1, provided superior postoperative analgesia when compared with IV sufentanil alone during desflurane anesthesia, without interfering with the ability to fast-track patients after cardiac surgery.

	Appendix 1

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Patient and nursing staff global assessment of pain management:

"Overall, would you rate the management of pain control during the first 24 hours after extubation as being poor, fair, good, or excellent?" Patient satisfaction questionnaire: "Was your sleep disturbed by the need to control your pain in the last 24 hours?" not at all; slightly; moderately; very; extremely "If you had the same operation again, would you ask for the same pain management?" definitely not; probably not; no preference; probably; definitely

	Footnotes

 
No reprints will be available.

	References

Top Abstract Introduction Methods Results Discussion Appendix 1 References

 

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